I love the interpretation of Pac-Man where he's a just a lowly worker retrieving golf balls left all over the course by the rich masters and the ghosts are all previous workers who got conked on the head and killed by incoming golf balls in the line of duty.

Oddball wrote:And movie Tony Stark should consider himself lucky. he only has that little arc reactor he wears. Back in the 60s when Ironman first appeared, he had to wear the entire chest plate constantly.

Some of my favorites:
Barbara Gordon, AKA Oracle, AKA my absolute favorite female in the DC Universe. Smart, redheaded, wears glasses, good with technology, and could beat your ass without getting off of hers. What's not to love?
Dr. Strangelove, from, well, Dr. Strangelove. "It should not be difficult, Mein Fuhrer... I mean Mr. President."
Destiny, from Marvel Comics. Blind, but could see into the future. Leading to a very funny moment when she left very specific instructions (location, time, direction to face, etc.) for Mystique to dispose of her ashes... which promptly blew right into Mystique's face.
Geordi La Forge, whom I'm honestly surprised no-one's mentioned yet.
Vitruvius, from The Lego Movie. (And Metalbeard too, really. "Really hard? Wipin' ye bum with a hook fer a hand is really hard!")

I recently started up playing Borderlands 2.Gaige, the Mechromancer is missing her left arm (though she did that to herself.); Krieg, the Psycho is not physically disabled, he's got a pretty bad case of Dissociative identity disorder (his original personality isn't in control of his body) and he shows symptoms of schizophrenia (he often makes random alliterations for no reason. In psychology, alliteration without logical association is often indicative of clanging, a symptom of schizophrenia). Also a fan-theory is he's blind in his right eye as it's covered up via an eyepatch-thing in his mask in his default skin.
Also, the same series running the gamut from mentally to physically (Generic Psychos and bandits are excluded):

Patricia Tannis - a VERY SEVERE case of Asperger's Syndrome.
Helena Pierce - Mechanical left arm, scarred left side of face and blind in that eye.
Wilhelm - His left arm and both legs are mechanical prosthesis. By Borderlands 2 he's more machine than man.
Tiny Tina - A severe case of PTSD
Sir Hammerlock - A Thresher by the name of Old Slappy tore out Hammerlock's arm at the socket. The same thresher also got the leg on that side, and possibly even the other leg as well. Also, he's missing his right eye.
Jimbo "Papa" Hodunk - He's missing his left leg and is normally confined to a wheelchair.
Handsome Jack - He's wearing a mask to hide his disfigurement that also rendered him blind in one eye.
Shade - Isolation-induced-insanity
Captain Scarlett - Mechanical eye

Crippled after having his legs crushed, he built himself a technological wheelchair. Just look at him, You can't tell me that's not a little awesome.

And he never blamed anyone for his disability, either. He felt a bit useless at first but he quickly worked it to his advantage. In fact, his friend, Murray blamed himself being unable to stop his best friend's from being handicapped, beating himself inside more then Bentley ever did.

Y'know, Team Fortress 2 has a few, starting with the Black Scottish Cyclops himself, the Demoman.
The Soldier is either mentally disabled or just really stupid (or both).
If you equip the right item, the Engineer has a prosthetic hand.
Not really a disability per se, but worth noting: Going by the events of Meet the Medic, all the characters have replacement hearts.
And of course, the Pyro does not look at the world the way anyone else does. (Makes Rin look normal, and that's saying something.)